Affiliation:
1. School of Pharmaceutical Sciences Guizhou University 550025 Guiyang China
2. Guizhou Engineering Laboratory for Synthetic Drugs 550025 Guiyang China
3. Technical Department of Criminal Investigation Branch Deyang Police Office 618000 Deyang China
Abstract
AbstractThe endoperoxide group of artemisinins is universally accepted an essential group for their anti‐cancer effects. In this study, a series of D‐ring‐contracted artemisinin derivatives were constructed by combining ring‐contracted artemisinin core with fragments of functional heterocyclic molecules or classical CDK4/6 inhibitors to identify more efficacious breast cancer treatment agents. Twenty‐six novel hybridized molecules were synthesized and characterized by HRMS, IR, 1H‐NMR and 13C NMR. In antiproliferative activities and kinase inhibitory effects assays, we found that the antiproliferative effects of B01 were close to those of the positive control Palbociclib, with GI50 values of 4.87±0.23 μM and 9.97±1.44 μM towards T47D cells and MDA‐MB‐436 cells respectively. In addition, the results showed that B01 was the most potent compound against CDK6/cyclin D3 kinase, with an IC50 value of 0.135±0.041 μM, and its activity was approximately 1/3 of the positive control Palbociclib.